| Literature DB >> 16137886 |
James Z Deng1, Daniel R McMasters, Philippe M A Rabbat, Peter D Williams, Craig A Coburn, Youwei Yan, Lawrence C Kuo, S Dale Lewis, Bobby J Lucas, Julie A Krueger, Berta Strulovici, Joseph P Vacca, Terry A Lyle, Christopher S Burgey.
Abstract
Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy.Entities:
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Year: 2005 PMID： 16137886 DOI： 10.1016/j.bmcl.2005.07.022
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823